Artículos (Farmacología, Pediatría y Radiología)
URI permanente para esta colecciónhttps://hdl.handle.net/11441/11030
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Artículo Clubs de lectura para estudiantes de máster y doctorado en ciencias de la salud: una experiencia de innovación docente(Editorial Universidad de Sevilla, 2025-06-03) Martin-Gisbert, Lucia; Ruano-Raviña, Alberto; García-González, Guadalupe; Rey-Brandariz, Julia; Candal-Pedreira, Cristina; Guerra-Tort, Carla; Fernández-Teijeiro, Ana; Pérez- Ríos, Mónica; Farmacología, Pediatría y RadiologíaIntroducción. Este trabajo expone una actividad denominada “Club de lectura de artículos científicos” para alumnado de Máster y Doctorado en el área de Epidemiología y Salud Pública en la Universidad de Santiago de Compostela (USC). Los objetivos fueron fomentar la reflexión y el pensamiento crítico de los asistentes ante problemas que son frecuentes o incipientes en el ámbito de la epidemiología y la salud pública. Método. En un primer momento, se anunció el cronograma de las sesiones del club de lectura planificadas, indicando el artículo a discutir y la persona encargada de ser ponente. Se enviaron recordatorios a los alumnos previos a cada sesión. Los ponentes fueron estudiantes de Doctorado o personal docente e investigador. Las sesiones fueron de asistencia eminentemente presencial en la Facultad de Medicina de la USC. Resultados. Se realizaron un total de 11 sesiones del club de lectura con entre 9 y 20 asistentes por sesión. Las temáticas tratadas fueron diversas, como el uso de inteligencia artificial en investigación, áreas de mejora de los cribados de cáncer, la mala conducta científica relacionada con revistas científicas y temas metodológicos, así como el uso de intervalos de confianza o la elaboración de cuestionarios epidemiológicos. Además, se realizó una encuesta de satisfacción a los participantes cuyos resultados fueron muy favorables. Conclusiones. Creemos que los clubs de lectura son una herramienta muy útil de innovación docente que permite cohesionar al alumnado, despertar la curiosidad científica y el espíritu crítico que deben tener las personas que se forman en investigación.Artículo Fatty acid composition of isoenergetic meals drives distinct postprandial immunometabolic responses in healthy adults: A randomized crossover pilot study(Elsevier, 2026-04) Márquez Parada, Elvira; Torrecillas López, María; Corell Almuraza, Alfredo; González de la Rosa, Teresa; Barrera Chamorro, Luna; Bermúdez Pulgarín, Beatriz; Claro Cala, Carmen María; Montserrat de la Paz, Sergio; Bioquímica Médica y Biología Molecular e Inmunología; Biología Celular; Farmacología, Pediatría y Radiología; Ministerio de Ciencia, Innovación y Universidades (MICIU). EspañaThe postprandial period represents a critical and dynamic phase during which dietary components can acutely influence metabolic and immune functions. While the chronic effects of dietary fat quality are well characterized, their immediate postprandial immunometabolic impact remains poorly understood. To investigate the acute effects of energy-matched test meals enriched in saturated (SFA), monounsaturated (MUFA), or omega-3 long-chain polyunsaturated fatty acids (ω3-LCPUFA), compared to a fat-free control, on systemic metabolic and immune parameters in healthy adults. In this randomized, crossover pilot study, ten healthy participants consumed four test meals separated by 2-week washouts. Blood samples were collected at fasting, 2–3 h (peak), and 5–6 h (late phase) postprandially. Biochemical and immunological biomarkers were assessed. Statistical analyses included two-way repeated-measures ANOVA, linear mixed models, and area under the curve (AUC/iAUC) calculations. MUFA- and ω3-LCPUFA-enriched meals induced significantly greater postprandial changes in glucose, triacylglycerides, LDL-C, and C-peptide compared to the SFA and fat-free meals, particularly at the late postprandial phase. These effects were confirmed by AUC and iAUC analyses. In contrast, although transient changes in immune cell counts and humoral markers were observed over time, no significant differences between fat types were detected in postprandial immune responses. In healthy adults, the fatty acid composition of energy-matched meals acutely modulates key metabolic pathways in a fat-type-specific manner, whereas systemic immune parameters remain largely unchanged. These preliminary findings suggest a functional dissociation between postprandial metabolic and immune response and underscore the need to more sensitive or compartment-specific immune readouts in future nutritional research.Artículo Evaluation of bone metabolism in children with cystic fibrosis(Elsevier, 2021-03-16) Mora Vallellano, Josefa; Delgado Pecellín, Carmen; Delgado Pecellín, Isabel; Quintana Gallego, María Esther; López-Campos Bodineau, José Luis; Farmacología, Pediatría y Radiología; Medicina; Instituto de Biomedicina de Sevilla (IBIS)Background Cystic fibrosis (CF) bone disease (CFBD) has attracted considerable recent interest from researchers, although several aspects of CFBD pathophysiology remain poorly understood. The objective of this research was to investigate CFBD in children with CF and its relation to clinical and bone metabolism markers. Methods In a prospective observational study of 68 patients with CF and 63 healthy controls, we studied bone turnover biomarkers and bone mineral density (BMD). The biomarkers included osteocalcin, total-alkaline phosphatase, bone-alkaline phosphatase, N-terminal propeptide of type-1-procollagen, osteoprotegerin (OPG), interleukine-6, tumor necrosis factor alpha (TNF-α), type-1-collagen cross-linked C-telopeptide (CTX), parathormone (PTH), 25-vitamin D, 1,25-vitamin D, calcium and phosphorus. BMD was examined in lumbar spine, comparing two healthy Spanish populations. Two regression analyses were applied to any significant associations to evaluate predictors of BMD and of CF, expressed as odds ratios (OR) with 95% confidence intervals. Results After adjusting for age, sex, and height Z-score, gains in BMD LS in children and adolescents (6–16 years) with CF were not less than in healthy reference population. Patients with CF showed significant associations with different bone turnover biomarkers. Age, gender, body mass index, PTH, CTX and OPG were significant predictors of BMD (R2 = 0.866, p < 0,001). Moreover, we found that PTH (OR = 1.070; 95% CI 1.019–1.123), and TNFα (OR = 2.173; 95% CI 1.514–3.118) were significantly linked to CF, and calcium (OR = 0.115; 95% CI 0.025–0.524), 1,25-vitamin D (OR = 0.979; 95% CI 0.962 0.996) and OPG (OR = 0.189; 95% CI 0.073–0.489) were significant reduced. Conclusion A normal bone mineral density along with altered remodeling was found in CF patients with a normal nutritional status and without acute lung disease.Artículo Distinct laboratory and clinical features of secondary hemophagocytic lymphohistiocytosis in pediatric visceral leishmaniasis: a retrospective analysis of 127 children in Andalusia, Spain (2004-2019)(Lippincott Williams & Wilkins, 2021-06) López Marcos, María; Ruiz Sáez, Beatriz; Vílchez Pérez, Juan Salvador; Moreno Pérez, David; Carazo Gallego, Begoña; Falcón Neyra, Lola; Obando Santaella, Ignacio; Neth, Olaf; Olbrich, Peter; GAIP (Grupo Andaluz de Infectología e Inmunopatología Pediátrica); Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III, Madrid, EspañaBackground: Visceral leishmaniasis (VL) is an endemic in Southern Europe. However, details regarding disease burden, clinical presentations, laboratory markers, management and outcome in children are scarce. Methods: Medical records of children (<14 years) admitted with VL to 10 pediatric units in Andalusia (2004–2019) were retrospectively reviewed. VL diagnosis was based on clinical presentation, serology, microscopy and molecular methods. Diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was established using the hemophagocytic lymphohistiocytosis-2004 criteria. Results: A total of 127 patients were identified. Median age was 14.5 months; the main clinical presentations were fever and splenomegaly (95.3% each). Cytopenias were the most common laboratory abnormalities. Diagnostics as well as treatment regimens varied over time and the participating centers. Liposomal amphotericin B was prescribed in 97.6%; relapses as well as adverse events were rarely observed (3.1% each). Thirty-seven patients, diagnosed with sHLH required longer hospital admission (P = 0.001), an increased number of platelet (P < 0.006) and red blood cell (P = 0.0001) transfusions and pediatric intensive care unit admission (P = 0.007). Monocytopenia (P = 0.011) and high C-reactive protein levels (P = 0.031), variables not included in the hemophagocytic lymphohistiocytosis-2004 criteria, were associated with sHLH. One patient deceased in the context of the Leishmania infection. Conclusions: We report data on the largest pediatric VL cohort from Europe, commonly associated with sHLH. Raised C-reactive protein levels and monocytopenia appear to be associated with sHLH. The latter may help to identify these patients and to guide decisions regarding need of additional supportive clinical care and immunomodulatory therapies. The observed high rate of heterogeneity in terms of diagnosis and management warrants the establishment of appropriate guidelines.Artículo JAK inhibitor treatment for inborn errors of JAK/STAT signaling: an ESID/EBMT-IEWP retrospective study(Mosby-Elsevier, 2023-11-05) Fischer, Marco; Olbrich, Peter; Hadjadj, Jérôme; Aumann, Volker; Bakhtiar, Shahrzad; Barlogis, Vincent; Speckmann, Carsten; Farmacología, Pediatría y Radiología; Bundesministerium fur Bildung und Forschung-BMBF; Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy (CIBSS); Instituto de Salud Carlos III; Research Fund of Istanbul University-CerrahpasaBackground: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events are limited. Objective: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers. Methods: We conducted a multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling who received JAKi treatment for at least 3 months. Results: Sixty-nine patients (72% children) were evaluated (45 STAT1 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 91% overall survival. Conclusions: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.Artículo Mortality From Cystic Fibrosis in Europe: 1994-2010(Wiley, 2015-11-19) Quintana-Gallego, Esther; Ruiz-Ramos, Miguel; Delgado Pecellín, Isabel; Calero, Carmen; Soriano, Joan B.; López-Campos Bodineau, José Luis; Farmacología, Pediatría y Radiología; MedicinaObjective: To date, available mortality trends due to cystic fibrosis (CF) have been limited to the analysis of certain countries in different parts of the world showing that mortality trends have been constantly decreasing. However, no studies have examined Europe as a whole. The present study aims to analyze CF mortality trends by gender within the European Union (EU) and to quantify potential years of life lost (PYLL). Design: Deaths from the 27 EU countries were obtained from the statistical office of the EU from the years 1994-2010. Crude and age-standardized mortality rates (ASR) were estimated for women and men using the standard European population, expressed in deaths per 1,000,000 persons. The PYLL from ages 0 up to 30 years were estimated. Trends were studied by a joinpoint regression analysis. Results: During the study period, 5,130 deaths (2,443 in males and 2,687 in females) were identified. Females had a slightly higher mortality rate than males, with a downward trend observed for both genders. In males, the ASR changed from 1.34 in 1994 to 1.03 in 2010. In females, the ASR changed from 1.42 in 1994 to 0.92 in 2010. The mean age at death and PYLL increased for both genders. The joinpoint analysis did not identify any significant joinpoint for either gender for ASR or PYLL. Conclusions: Our data suggest a continued downward trend of CF mortality throughout the EU, with differences by country and gender.Artículo Resultados del programa de screening neonatal de fibrosis quística en Andalucía tras 5 años de su implantación(Ediciones doyma S A; Elsevier España SLU; Elsevier doyma SL, 2018) Delgado Pecellín, Isabel; Pérez Ruiz, Estela; Álvarez Ríos, Ana Isabel; Delgado Pecellín, Carmen; Yahyaoui Macías, Raquel; Carrasco Hernández, Laura; Quintana Gallego, María Esther; Farmacología, Pediatría y RadiologíaIntroducción Andalucía dispone de screening neonatal de fibrosis quística (SNFQ) desde mayo 2011, basado en doble determinación de tripsinógeno inmunorreactivo ([TIR] [TIR1/TIR2]). Si el screening es positivo realizamos un test del sudor y si es positivo o dudoso solicitamos genética. Objetivo Analizar el SNFQ, basado en los resultados de los primeros 4,5 años. Material y método Estudio descriptivo prospectivo de los neonatos sometidos a SNFQ. Se recogen los niveles de TIR, cloruro en sudor, mutaciones. Mediante SPSS12.0 se realizó análisis estadístico. Resultados Desde mayo 2011 a diciembre 2016, 474.953 neonatos fueron sometidos a SNFQ. Mil ochenta y siete (0,23%) presentaron TIR2 elevado. Desde la implantación del SNFQ se diagnosticaron 73 casos con fibrosis quística; 60 de ellos fueron diagnosticados mediante un SNFQ positivo, mientras que 13 no. Concretamente un paciente comenzó con clínica clásica de fibrosis quística y se comprobó que no se había realizado el SNFQ por decisión paterna; los 12 restantes tuvieron un SNFQ negativo (falsos negativos). De estos, un paciente fue diagnosticado presintomáticamente al tener su hermano gemelo con SNFQ positivo; otro con cloruro en el límite alto de la normalidad se diagnosticó presintomáticamente mediante genética; 10 pacientes comenzaron clínicamente. Excluyendo los pacientes con íleo meconial, la sensibilidad y especificidad del programa de SNFQ asciende al 85,71 y 99,78% respectivamente. La incidencia de la enfermedad en Andalucía es de 1/6.506 recién nacidos vivos. Conclusión Los presentes resultados nos permiten reflexionar sobre posibles áreas de mejoras adicionales del algoritmo del SNFQ, que debe pasar por la introducción de estudios genéticos para así aumentar la sensibilidad y disminuir los falsos positivos.Artículo Meningoencephalitis due to adenovirus in a healthy infant mimicking severe bacterial sepsis(Lippincott williams & wilkins, 2014) Reyes-Andrade, J; Sánchez-Céspedes, Javier; Olbrich, Peter; Falcon, L; Sanchez-Ganfornina, I; Tebruegge, M; Perez-Romero, P; Neth, Olaf; Farmacología, Pediatría y Radiología; Andalucía Salud; Instituto de Salud Carlos III; Instituto Nacional de Investigación en Salud; Plan Nacional de I+D+i; Ministerio de Bienestar Social; Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia y Competitividad, Spanish Network for Research in Infectious DiseasesWe present the case of a previously healthy 15-month-old girl with acute adenovirus infection who had features of severe bacterial sepsis and meningitis. Real-time qPCR done on cerebrospinal fluid identified adenovirus as the causative agent allowing stopping antibiotic treatment. The patient subsequently recovered without sequelae. An overview of published and unpublished data on adenovirus central nervous system infection in immunocompetent children is presented.Artículo Clinical and immunological impact of JAK inhibition in concurrent Down syndrome and STAT1 gain of function(Springer, 2025-11-25) Blanco Lobo, Pilar; Gilabert-Prieto, Paula; De Felipe, Beatriz; Moreno-Fuentes, David; Guisado Hernández, Paloma; Ortiz-Ramírez, Ana; Cordero Matia, María Elisa; Olbrich, Peter; Neth, Olaf; Farmacología, Pediatría y RadiologíaDown syndrome (DS) and STAT1 gain-of-function (GOF) share clinical and molecular features, including persistent inflammation. We aimed to investigate whether the coexistence of DS and a STAT1 GOF mutation in a patient synergistically enhances interferon (IFN) signaling and exacerbates inflammatory responses, posing additional management challenges. Two patients (P1 and P2) were studied: P1, with DS and a heterozygous p.P326S STAT1 variant, and P2, with the STAT1 p.P326S variant only. Individuals with isolated DS or STAT1 GOF served as controls. IFN receptor subunits (IFNγR1/R2 and IFNαR1/R2) and responses to IFNα/γ stimulation were analyzed using flow cytometry and RT-PCR. Whole blood type I IFN signature and serum cytokines were evaluated using NanoString and Luminex assays. P1 experienced recurrent infections, chronic mucocutaneous candidiasis, interstitial pneumonitis, and pulmonary hypertension. P2 presented with esophageal candidiasis, dysphagia, and stenosis. The p.P326S variant led to increased STAT1/pSTAT1 levels in response to IFNα/γ. Both patients showed significant clinical improvement with the Janus kinase (JAK) inhibitor ruxolitinib. However, P1's key biomarkers (STAT1 levels, IFN signature, TNFα, IL-6) remained altered, indicating persistent inflammation despite clinical improvement. This first report of a STAT1 GOF variant in DS provides a unique "experiment of nature", offering insights into the interplay between trisomy 21 and STAT1-mediated immune dysregulation. Although ruxolitinib demonstrated clinical benefits, the persistent inflammation observed in P1 highlights the need for further strategies to achieve complete immune resolution. These findings emphasize the importance of comprehensive genetic and immunological assessments in individuals with DS, particularly when immune dysfunction is suspected.Artículo Statistical evaluation of metaproteomics and 16S rRNA amplicon sequencing techniques for study of gut microbiota establishment in infants with cystic fibrosis(American Society for Microbiology, 2022-10-18) Saralegui, Claudia; García-Durán, Carmen; Romeu, Eduardo; Hernáez-Sánchez, María Luisa; Maruri, Ainhize; Bastón-Paz, Natalia; Delgado Pecellín, Isabel; Del Campo, Rosa; Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III; Unión Europea; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)Newborn screening for cystic fibrosis (CF) can identify affected but asymptomatic infants. The selection of omic technique for gut microbiota study is crucial due to both the small amount of feces available and the low microorganism load. Our aims were to compare the agreement between 16S rRNA amplicon sequencing and metaproteomics by a robust statistical analysis, including both presence and abundance of taxa, to describe the sequential establishment of the gut microbiota during the first year of life in a small size sample (8 infants and 28 fecal samples). The taxonomic assignations by the two techniques were similar, whereas certain discrepancies were observed in the abundance detection, mostly the lower predicted relative abundance of Bifidobacterium and the higher predicted relative abundance of certain Firmicutes and Proteobacteria by amplicon sequencing. During the first months of life, the CF gut microbiota is characterized by a significant enrichment of Ruminococcus gnavus, the expression of certain virulent bacterial traits, and the detection of human inflammation-related proteins. Metaproteomics provides information on composition and functionality, as well as data on host-microbiome interactions. Its strength is the identification and quantification of Actinobacteria and certain classes of Firmicutes, but alpha diversity indices are not comparable to those of amplicon sequencing. Both techniques detected an aberrant microbiota in our small cohort of infants with CF during their first year of life, dominated by the enrichment of R. gnavus within a human inflammatory environment. IMPORTANCE In recent years, some techniques have been incorporated for the study of microbial ecosystems, being 16S rRNA gene sequencing being the most widely used. Metaproteomics provides the advantage of identifying the interaction between microorganisms and human cells, but the available databases are less extensive as well as imprecise. Few studies compare the statistical differences between the two techniques to define the composition of an ecosystem. Our work shows that the two methods are comparable in terms of microorganism identification but provide different results in alpha diversity analysis. On the other hand, we have studied newborns with cystic fibrosis, for whom we have described the establishment of an intestinal ecosystem marked by the inflammatory response of the host and the enrichment of Ruminococcus gnavus.Artículo Human gut microbiota analysis of cystic fibrosis infants using metaproteomics(American Society for Microbiology, 2024-07-05) García-Durán C.; Saralegui C.; Romeu E.; Hernáez M.L.; Maruri, A.; Bastón-Paz, N.; Delgado Pecellín, Carmen; Gil, C.; Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III; Unión Europea; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Comunidad de MadridWe report a metaproteomic analysis of the gut microbiota of eight infants with cystic fibrosis, during the first year of life. This is the first study in this disease that uses metaproteomics to analyze stool samples from patients at such a young age.Artículo Evaluation of alpha1 antitrypsin deficiency-associated mutations in people with cystic fibrosis(MDPI, 2025-09-25) López-Campos Bodineau, José Luis; García Tamayo, Pedro; Girón, Maria Victoria; Delgado Pecellín, Isabel; Olveira, Gabriel; Carrasco, Laura; Quintana-Gallego, Esther; Medicina; Farmacología, Pediatría y RadiologíaBackground: Recent hypotheses suggest that mutations associated with alpha1 antitrypsin (AAT) deficiency (AATD) may influence the clinical presentation and progression of cystic fibrosis (CF). This study employs a longitudinal design to determine the prevalence of AATD mutations and assess their impact on CF. Methods: The study Finding AAT Deficiency in Obstructive Lung Diseases: Cystic Fibrosis (FADO-CF) is a retrospective cohort study evaluating people with CF from November 2020 to February 2024. On the date of inclusion, serum levels of AAT were measured and a genotyping of 14 mutations associated with AATD was performed. Historical information, including data on exacerbations, microbiological sputum isolations, and lung function, was obtained from the medical records, aiming at a temporal lag of 10 years. Results: The sample consisted of 369 people with CF (40.9% pediatrics). Of these, 58 (15.7%) cases presented at least one AATD mutation. The AATD allelic combinations identified were PI*MS in 47 (12.7%) cases, PI*MZ in 5 (1.4%) cases, PI*SS in 3 (0.8%) cases, PI*SZ in 2 (0.5%) cases, and PI*M/Plowell in 1 (0.3%) case. The optimal cutoff value for AAT levels to detect AATD-associated mutation carriers was 129 mg/dL in the overall cohort (sensitivity of 73.0%; specificity 69.2%) and 99.5 mg/dL when excluding PI*MS cases (sensitivity 98.0%; specificity 90.9%), highlighting the need for lower thresholds in clinically severe genotypes to improve case detection. The number of mild exacerbations during the follow-up appeared to be associated with AATD mutations. Conclusions: AATD mutations are prevalent in CF and may impact certain clinical outcomes. If systematic screening was to be planned, we recommend considering the proposed cut-off points to select the population for genetic studies.Artículo Exposure to mixed metals/metalloids in early childhood: a cross-sectional cohort study in children from Sevilla, Southern Spain(Elsevier, 2025-10-13) Quintana-Mejía, María; Hinojosa Hidalgo, María Gracia; Garrido, Ana I.; González, Marta; Millán Jiménez, Antonio; Acosta Gordillo, L.; Periañez, Ángela; Moreno Navarro, Isabel María; Nutrición y Bromatología, Toxicología y Medicina Legal; Farmacología, Pediatría y Radiología; AGR258: Alimentos Funcional es e Investigación Toxicológica; HUM965: Transhumancias: Hábitat, Salud, Patrimonio, Tecnología y ArteThe synergy of exposure to neurotoxic substances, including some metals and metalloids has emerged as a global concern due to its effects on neurodevelopment. Thus, this study determined the presence of Al, Cr, Mn, Ni, Cu, Zn, As, Se, Cd, and Pb in hair and their relationship with the developmental profile in a cohort of 254 children at 6, 12, 18, and 24 months of age in Seville, Southern Spain. A cross-sectional examination was conducted, including the measurement of metal-metalloid levels in hair using mass spectrometric analysis with inductively coupled plasma (ICP-MS). The children's developmental profile was assessed using the Battelle Developmental Inventory (BDI). The results showed that each hair sample contained 2 to 10 metals or metalloids. A multiple regression analysis found that a model including all elements—along with factors such as age, number and levels of detected metals/metalloids, maternal education, and developmental measures—was significantly associated with overall development (BDI score) as well as the personal-social, cognitive, and language domains. In this sense, Pb, Al, Mn and As were demonstrated to be the elements with more negative correlations to the different parameters. The interaction effects of metal-metalloid mixtures reinforce global concerns about their differentiated impacts on early childhood, depending on sex and the affected developmental domain. These findings are alarming due to their potential implications as predictors of developmental deficits, psychomotor skills, and future school performance. Thus, environmental surveillance and infant biomonitoring in non-industrial urban settings, such as Seville, highlight the need to redefine territorial strategies for reducing everyday environmental pollutants. This study underscores the importance of addressing invisible chronic exposures and identifying social determinants that modulate neurotoxicity and neurodevelopmental disorders.Artículo Impact of recommended maternal vaccination programs on the clinical presentation of sars-cov-2 infection: A prospective observational study(MDPI, 2021-01-08) Quintana-Mejía, María; Hinojosa Hidalgo, María Gracia; Garrido, Ana I.; González, Marta; Millán Jiménez, Antonio; Acosta Gordillo, L.; Periañez, Ángela; Moreno Navarro, Isabel María; Nutrición y Bromatología, Toxicología y Medicina Legal; Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III-Ministerio de Sanidad; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); AGR258: Alimentos Funcional es e Investigación Toxicológica; HUM965: Transhumancias: Hábitat, Salud, Patrimonio, Tecnología y ArteThe COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. A total of 1150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.Artículo Expanding the clinical and mutational spectrum of germline ABL1 mutations-associated syndrome: A case report(Lippincott, Williams & Wilkins, 2019-03) Bravo Gil, Nereida Inés; Marcos, Irene; González-Meneses López, Antonio; Antiñolo Gil, Guillermo; Borrego, Salud; Cirugía; Farmacología, Pediatría y Radiología; CIBERER ACCI; European Union (UE); Instituto de Salud Carlos III; Junta de AndalucíaRationale: Clinical and genetic management of patients with rare syndromes is often a difficult, confusing, and slow task. Patient concerns: Male child patient with a multisystemic disease showing congenital heart defects, facial dysmorphism, skeletal malformations, and eye anomalies. Diagnosis: The patient remained clinically undiagnosed until the genetic results were conclusive and allowed to associate its clinical features with the germline ABL1 mutations-associated syndrome. Interventions: We performed whole-exome sequencing to uncover the underlying genetic defect in this patient. Subsequently, family segregation of identified mutations was performed by Sanger sequencing in all available family members. Outcomes: The only detected variant compatible with the disease was a novel heterozygous nonframeshift de novo deletion in ABL1 (c.434_436del; p.Ser145del). The affected residue lays in a functional domain of the protein, it is highly conserved among distinct species, and its loss is predicted as pathogenic by in silico studies. Lessons: Our results reinforce the involvement of ABL1 in clinically undiagnosed cases with developmental defects and expand the clinical and genetic spectrum of the recently reported ABL1-associated syndrome. In this sense, we described the third germline ABL1 causative mutation and linked, for the first time, ocular anterior chamber anomalies to this pathology. Thus, we suggest that this disorder may be more heterogeneous than is currently believed and may be overlapping with other multisystemic diseases, hence genetic and clinical reassessment of this type of cases should be considered to ensure proper diagnosis.Artículo Prognostic significance of mutation type and chromosome fragility in Fanconi anemia(Wiley, 2024-11-19) Ramírez, María José; Pujol, Roser; Minguillón, Jordi; Bogliolo, Massimo; Persico, Ilaria; Cavero, Débora; Fernández-Teijeiro, Ana; Surrallés, Jordi; Farmacología, Pediatría y Radiología; Gobierno de España; Instituto de Salud Carlos III; European Union (UE); Generalitat de CatalunyaFanconi anemia (FA) is a rare genetic disease characterized by high phenotypic and genotypic heterogeneity, and extreme chromosome fragility. To better understand the natural history of FA, identify genetic risk and prognostic factors, and develop novel therapeutic strategies, the Spanish Registry of Patients with FA collects data on clinical features, chromosome fragility, genetic subtypes, and DNA sequencing with informed consent of participating individuals. In this article, we describe the clinical evolution of 227 patients followed up for up to 30 years, for whom our data indicate a cumulative cancer incidence of 86% by age 50. We found that patients with lower chromosome fragility had a milder malformation spectrum and better outcomes in terms of later-onset hematologic impairment, less severe bone marrow failure, and lower cancer risk. We also found that outcomes were better for patients with mutations leading to mutant FANCA protein expression (genetic hypomorphism) than for patients lacking this protein. Likewise, prognosis was consistently better for patients with biallelic mutations in FANCD2 (mainly hypomorphic mutations) than for patients with biallelic mutations in FANCA and FANCG, with the lack of the mutant protein in patients with biallelic mutations in FANCG contributing to their poorer outcomes. Our results regarding the clinical impact of chromosome fragility and genetic hypomorphism suggest that mutant FA proteins retain residual activity. This finding should encourage the development of novel therapeutic strategies aimed at partially or fully enhancing mutant FA function, thereby preventing or delaying bone marrow failure and cancer in patients with FA.Artículo Safety and efficacy of immunoguided prophylaxis for cytomegalovirus disease in low-risk lung transplant recipients in Spain: a multicentre, open-label, randomised, phase 3, noninferiority trial(Elsevier, 2025-03-26) Páez Vega, Aurora; Vaquero Barrios, José M.; Ruiz Arabi, Elisa; Iturbe Fernández, David; Alonso, Rodrigo; Ussetti Gil, Piedad; Lobo Acosta, María Ángeles; Gutiérrez Gutiérrez, Belén; Torre Cisneros, Julián; Medicina; Farmacología, Pediatría y Radiología; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red (CIBER); European Union (UE); Gobierno de España; Sociedad Andaluza de Trasplante de Órganos y Tejidos (SATOT)Background: The standard prophylaxis treatment for cytomegalovirus (CMV) disease in CMV-seropositive lung transplant recipients is six months of prophylaxis with valganciclovir followed by six months of pre-emptive therapy. This protocol is associated with adverse events and risk of resistance. We have previously shown that prophylaxis can be suspended in CMV-seropositive kidney transplant recipients receiving thymoglobulin without increasing the risk of CMV disease and reducing the incidence of neutropenia. The objective of the current study is to demonstrate that immunoguided prophylaxis is effective and safe in seropositive lung transplant recipients. Methods: A phase III, multicentre, randomised, open-label, noninferiority clinical trial was conducted in adult lung transplant recipients. Patients were randomised (1:1) to two groups: (1) immunoguided prophylaxis (IP), consisting of 3 months of universal prophylaxis followed by CMV-specific cell-mediated immunity-guided discontinuation, or (2) standard prophylaxis (SP), consisting of 6 months of prophylaxis followed by pre-emptive therapy, both for a total of 12 months. The noninferiority margin was 7%. The primary and secondary efficacy endpoints were CMV disease and asymptomatic CMV replication at month 18. The primary and secondary safety endpoints were incidence of neutropenia (defined as neutrophil count <1500 cells/μL), incidence of rejection and number of days of valganciclovir prophylaxis. This trial was registered in EudraCT (2018-003300-39) and ClinicalTrials.gov (NCT03699254). This trial has been completed. Findings: Patients were recruited between April 2019 and December 2021 in seven Spanish centres. A total of 150 patients were randomised (75 patients per group). Incidence of CMV disease at month 18 did not differ among groups (18·7% [14 patients] vs. 16·0% [12 patients]; risk difference [RD] −0·03 [95% CI −0·15% to 0·06%]; P = 0·620) but occurred earlier in the IP group compared to the SP group. The proportion of patients who developed CMV disease at ≤180 days after transplant was higher in the IP group compared with the SP group (8% [6 patients] vs. 0% [0 patients]; RD −0·08 [95% CI −0·14 to −0·02; P = 0·009]). Asymptomatic CMV replication was reduced in the IP group vs. the SP group (4·0% [3 patients] vs. 16·0% [12 patients]; adjusted RD 0·12 [95% CI 0·03–0·21; P = 0·009]). A total of 30 patients (40%) in the IP group did not require prophylaxis from month 4 to 12. No significant difference was observed in the proportion of patients with neutropenia during months 4 to 7 (14·7% [11 patients] vs. 25·3% [19 patients]; RD 0·11 [95% CI −0·02 to 0·23]; P = 0·090) or rejection (33·3% [25 patients] vs. 30·7% [23 patients]; RD −0·03 [95% CI −0·18 to 0·12; P = 0·690]). The median days of valganciclovir was lower in the IP group than in the SP group (137 [92–266] vs. 198 [173–281]; P < 0.001). Interpretation: Immunoguided prophylaxis was noninferior to the standard of care in preventing CMV disease in lung transplant recipients. It could be considered for implementing in clinical practice in CMV-seropositive lung transplant recipients upon considering the study limitations.Artículo Grave retraso del neurodesarrollo y estatura en niña inmigrante(2024-11-24) García García, Emilio José; Alonso Luengo, Olga; Sobrino Toro, Manuel; Farmacología, Pediatría y RadiologíaPresentamos una niña recién llegada de Marruecos, país sin acceso a cribado neonatal, que consulta con nueve años en la urgencia hospitalaria por grave retraso global de neurodesarrollo y enanismo. Los padres referían estreñimiento crónico y que consiguió control cefálico y sedestación con cuatro años, bipedestación con siete, con nueve estaba dando sus primeros pasos y aún no hablaba. Presentaba talla 90 cm (percentil < 1, -7,6 desviación estándar (DE), peso 15 kg (pc < 1, -2,55 DE), índice de masa corporal 18,5 kg/m2 (pc 55, +0,15 DE), hipoacusia, mixedema facial, macroglosia, labios prominentes, falta de la cola de las cejas, distensión abdominal, hernia umbilical, hiporreflexia y contractura en flexión de los miembros inferiores (fig. 1). Se diagnosticó de agenesia tiroidea con tiroxina libre < 0,08 ng/dL, tirotropina > 1.000 mU/L, tiroglobulina < 0,04 ng/mL y ausencia de captación en la gammagrafía. Se observó también aumento del LDL-colesterol (185 mg/dL). Con levotiroxina oral el hábito intestinal, contracturas y deambulación mejoraron y el mixedema y la hipercolesterolemia desaparecieron. (extracto)Artículo Síndrome de Ondine. A propósito de un caso(Elsevier, 2023-10) León Carretero, Susana; Román Fernández, Ana; González Barreda, Carmen; Campo Barasoain, Andrea; Granero Asencio, Mercedes; Farmacología, Pediatría y RadiologíaRecién nacida a término, sin antecedentes prenatales de interés, ni factores de riesgo infeccioso. Presenta parto inducido por enfermedad materna con amniorrexis de 8 h de evolución que da lugar a líquido meconial espeso, finalizando mediante ventosa para abreviar expulsivo. Nace con test Apgar: 8/9/9 y pH cordón 7,34, precisando aspiración de secreciones, y ventilación con presión positiva intermitente en el primer minuto de vida, con evolución favorable, pero necesitando oxígeno suplementario para mantener adecuada saturación, por lo que ingresa en la Unidad Neonatal. (extracto)Carta al Director Síndrome tricorrinofalángico: un diagnóstico de visu al alcance del pediatra(Elsevier, 2023-12) Cortés Jiménez, María del Carmen; Fernández García, Raquel María; García García, Emilio José; Farmacología, Pediatría y RadiologíaEl síndrome tricorrinofalángico (TRPS) es una entidad poco frecuente de herencia autosómica dominante, alta penetrancia y expresividad variable, que se debe a una alteración en el gen TRPS1. Clínicamente se caracteriza por alteraciones del pelo (cabello escaso, adelgazamiento lateral de las cejas) y uñas (distrofia ungueal), leve dismorfia facial (punta nasal bulbosa, filtrum largo y plano, labio superior fino y pabellones auriculares prominentes) y anomalías esqueléticas (talla baja, braquidactilia, desviación de las falanges, epífisis de las falanges en forma de cono, displasia de caderas y osteopenia). Se subdivide en dos tipos: TRPS I (OMIM # 190350), que se debe a variantes patogénicas del gen TRPS1; y TRPS II (OMIM # 150230), que se produce por deleción de genes contiguos en el cromosoma 8 (incluyendo TRPS1 y EXT1) y asocia además osteocondromas y discapacidad intelectual. (extracto)